Phage display is a powerful in vitro evolution technology that enables rare ligands with desired characteristics to be isolated from large libraries of variants encoded by and expressed at the surface of filamentous bacteriophage. Many antibodies identified via phage display are currently used therapeutically or are in clinical development. While antibody phage display has been used to discover bispecific antibodies to date, the process has not streamlined to insure that selection is based on co-engagement. Moreover, other techniques known in the art (e.g., phage diabody technology) have not been used for direct selection based on co-engagement and broader application of phage diabody technology may not be possible due to difficulties in constructing diabody repertoires. Differences in the antigen binding site geometry of diabodies versus immunoglobulin molecules may compromise their utility for translation into immunoglobulin-based bispecific antibody formats.
Thus, there exists a need for phage display compositions and methods that allow for pairs of antibodies to be co-selected based on co-engagement of their respective targets.